The Ia antigens found on murine lymphocytes and macrophages are encoded by loci in the H-2 major histocompatibility gene complex and are thought to play a role in the induction and regulation of immune responses. The goal of our research is to elucidate details of the genetics, structure, and expression of Ia antigens which will help us to understand what their role is in the control of immune responsiveness. This coming year we plan to continue our studies of the invariant Ia antigen-associated (Ii) chain to determine the subcellular localization of the chain and to try to map its structural gene. We also will extend our studies of the variable expression of Ia antigens, concentrating on the analysis of mixed-haplotype alpha and beta chain Ia complexes on cell surfaces. Finally, we hope to select variant cell lines expressing altered Ia antigens using a number of immunoselection procedures. This project should yield information about the types and frequency of mutation at Ia loci, the pathways of biosynthesis and processing of Ia antigens, and the sites of alloantigenic determinants on Ia molecules.